ABSTRACT
Uterine leiomyomas are the most common benign gynecologic tumors. While the true etiology of leiomyomas remains unknown, their origin is thought to be multifactorial including genetic, hormonal, and tissue growth factor variations. Leiomyomas are predominantly found in women of reproductive age and are the leading indication for hysterectomy worldwide. Menstrual irregularities, pain, and fertility difficulties may arise from leiomyoma presence, although many women remain asymptomatic. Diagnosis can be made via ultrasound or magnetic resonance imaging, when precise mapping of the tissue is needed. Many treatment options are available ranging from surgical to medical and should be chosen depending on symptom severity, number and size of leiomyomas, patient age, fertility desires, and patient preferences. The objective of this article is to present a practical clinical perspective on uterine leiomyomas and an overview of contemporary treatment options.
Subject(s)
Leiomyoma/diagnosis , Leiomyoma/therapy , Reproductive Health , Uterine Neoplasms/diagnosis , Uterine Neoplasms/therapy , Age Factors , Antineoplastic Agents/therapeutic use , Female , Growth Inhibitors/therapeutic use , Humans , Hysterectomy , Leiomyoma/etiology , Prognosis , Receptors, Growth Factor/antagonists & inhibitors , Risk Factors , Treatment Outcome , Uterine Neoplasms/etiologyABSTRACT
Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and helper T cells, natural killer cells, granulocytes, and monocytes using whole genome microarrays. A bioinformatics analysis of these data was performed focusing on transcription factors, immunoglobulin superfamily members, and lineage-specific transcripts. We observed that the numbers of lineage-specific genes varies by 2 orders of magnitude, ranging from 5 for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel coexpression patterns for key transcription factors involved in hematopoiesis (eg, GATA3-GFI1 and GATA2-KLF1). This study represents the most comprehensive analysis of gene expression in hematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which are freely accessible, will be invaluable for future studies on hematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.
Subject(s)
Bone Marrow Cells/physiology , Cell Differentiation/genetics , Gene Expression , Atlases as Topic , Cell Lineage , Cells, Cultured , Flow Cytometry , Gene Expression Profiling , Hematopoiesis , Humans , Oligonucleotide Array Sequence Analysis , Transcription Factors/metabolismABSTRACT
DNA sequence variants in specific genes or regions of the human genome are responsible for a variety of phenotypes such as disease risk or variable drug response. These variants can be investigated directly, or through their non-random associations with neighbouring markers (called linkage disequilibrium (LD)). Here we report measurement of LD along the complete sequence of human chromosome 22. Duplicate genotyping and analysis of 1,504 markers in Centre d'Etude du Polymorphisme Humain (CEPH) reference families at a median spacing of 15 kilobases (kb) reveals a highly variable pattern of LD along the chromosome, in which extensive regions of nearly complete LD up to 804 kb in length are interspersed with regions of little or no detectable LD. The LD patterns are replicated in a panel of unrelated UK Caucasians. There is a strong correlation between high LD and low recombination frequency in the extant genetic map, suggesting that historical and contemporary recombination rates are similar. This study demonstrates the feasibility of developing genome-wide maps of LD.
